This application is concerned with the continuing support of the Joseph P. Kennedy, Jr. Mental Retardation Research Center at the University of Chicago. The research in this Center is a coordinated effort to study the problems of mental retardation from a basic science and clinical point of view. The proposed basic science programs include studies in the areas of biochemistry, genetics, neurobiology, developmental biology and virology. Major research projects are in the following areas: (1) Fundamental studies to delineate the chemistry, biosynthesis and physiology of acid mucopolysaccharides and glycolipids. Within this context, work is in progress to determine some metabolic abnormalities which are responsible for genetically determined diseases that result in mental retardation. Recently this work has been greatly facilitated by the use of the fibroblast culture technique to provide large amounts of living material for biochemical study. This technique has also allowed the work to be expanded into studies of lipid storage diseases. (2) Studies on the correlation of dendritic changes in brains of patients with mental retardation. Morphologic and biochemical studies are carried out following restricted destructive lesions particularly in the central nervous system. These studies are undertaken to provide some basis for understanding the sequelae of naturally occurring neural lesions. A new phase of the studies will be an analysis of the effects of lesions in the developmental period. (3) Studies of virus induced cellular transformations as a model for one mechanism for the production of cellular abnormalities which may result in mental retardation. (4) Studies of the mechanisms of cellular differentiation. These investigations are particularly aimed at acquiring an understanding of the normal mechanisms of differentiation and those influences which interfere with these normal processes with resultant developmental abnormalities.